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Synthesis, crystal structure, insecticidal activities, molecular docking and QSAR studies of some new phospho guanidines and phospho pyrazines as cholinesterase inhibitors.
Pestic Biochem Physiol 2019; 157:122-137PB

Abstract

Novel phospho guanidine and phospho pyrazine derivatives were synthesized and characterized by 31P, 13C, 1HNMR and IR spectroscopy to obtain novel and human-safe insecticides. Compound 35 [(C4H4N2NH)2P(O)(C6H6)] was investigated by X-ray crystallography. The inhibitory effects of synthesized compounds were evaluated on human and insect acetylcholinesterase (AChE) using in vitro Ellman method. A few of these compounds, which had low human toxicity, were selected for assessing the killing effects (in vivo) on the elm leaf beetle (X.luteola). The in vitro and in vivo results indicated that compounds bearing both phosphoryl groups and aromatic systems were found to possess a good selectivity for the inhibition of insect AChE over human AChE; up to 550-fold selectivity was achieved for compound 19. Docking studies were performed to explain reasons for the selective behavior of AChE inhibitors. Additionally, the quantitative structure-activity relationship (QSAR) and density functional theory (DFT) results of AChEs demonstrated that the size, shape, dipole moment, and ability to form hydrogen bond played the main role in both models. In addition, the aromatic π - π interactions and charge of the amide nitrogen had a major effect on insecticidal activity of the compounds. The present research can be helpful to gain a better understanding of the interactions between the insect AChE and its inhibitors and introduces compounds which are capable of becoming human-safe insecticides.

Authors+Show Affiliations

Department of Chemistry, Tarbiat Modares University, Tehran, Iran. Electronic address: gholi_kh@modares.ac.ir.Department of Chemistry, Tarbiat Modares University, Tehran, Iran.Department of Chemistry, Tarbiat Modares University, Tehran, Iran.Department of Chemistry, Tarbiat Modares University, Tehran, Iran.Department of plant protection, Agricultural and Natural Resources Research Center, ARREO, Gorgan, Iran.Department of Chemistry, Tarbiat Modares University, Tehran, Iran.Department of Chemistry, Tarbiat Modares University, Tehran, Iran.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31153459

Citation

Gholivand, Khodayar, et al. "Synthesis, Crystal Structure, Insecticidal Activities, Molecular Docking and QSAR Studies of some New Phospho Guanidines and Phospho Pyrazines as Cholinesterase Inhibitors." Pesticide Biochemistry and Physiology, vol. 157, 2019, pp. 122-137.
Gholivand K, Mohammadpanah F, Pooyan M, et al. Synthesis, crystal structure, insecticidal activities, molecular docking and QSAR studies of some new phospho guanidines and phospho pyrazines as cholinesterase inhibitors. Pestic Biochem Physiol. 2019;157:122-137.
Gholivand, K., Mohammadpanah, F., Pooyan, M., Valmoozi, A. A. E., Sharifi, M., Mani-Varnosfaderani, A., & Hosseini, Z. (2019). Synthesis, crystal structure, insecticidal activities, molecular docking and QSAR studies of some new phospho guanidines and phospho pyrazines as cholinesterase inhibitors. Pesticide Biochemistry and Physiology, 157, pp. 122-137. doi:10.1016/j.pestbp.2019.03.010.
Gholivand K, et al. Synthesis, Crystal Structure, Insecticidal Activities, Molecular Docking and QSAR Studies of some New Phospho Guanidines and Phospho Pyrazines as Cholinesterase Inhibitors. Pestic Biochem Physiol. 2019;157:122-137. PubMed PMID: 31153459.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Synthesis, crystal structure, insecticidal activities, molecular docking and QSAR studies of some new phospho guanidines and phospho pyrazines as cholinesterase inhibitors. AU - Gholivand,Khodayar, AU - Mohammadpanah,Fahimeh, AU - Pooyan,Mahsa, AU - Valmoozi,Ali Asghar Ebrahimi, AU - Sharifi,Mahboobeh, AU - Mani-Varnosfaderani,Ahmad, AU - Hosseini,Zahra, Y1 - 2019/03/16/ PY - 2019/02/02/received PY - 2019/03/10/revised PY - 2019/03/14/accepted PY - 2019/6/3/entrez PY - 2019/6/4/pubmed PY - 2019/6/14/medline KW - Acetylcholinesterase inhibitors KW - Docking KW - Human-safe insecticides, elm leaf beetle KW - Phospho guanidine KW - Phospho pyrazine KW - QSAR SP - 122 EP - 137 JF - Pesticide biochemistry and physiology JO - Pestic Biochem Physiol VL - 157 N2 - Novel phospho guanidine and phospho pyrazine derivatives were synthesized and characterized by 31P, 13C, 1HNMR and IR spectroscopy to obtain novel and human-safe insecticides. Compound 35 [(C4H4N2NH)2P(O)(C6H6)] was investigated by X-ray crystallography. The inhibitory effects of synthesized compounds were evaluated on human and insect acetylcholinesterase (AChE) using in vitro Ellman method. A few of these compounds, which had low human toxicity, were selected for assessing the killing effects (in vivo) on the elm leaf beetle (X.luteola). The in vitro and in vivo results indicated that compounds bearing both phosphoryl groups and aromatic systems were found to possess a good selectivity for the inhibition of insect AChE over human AChE; up to 550-fold selectivity was achieved for compound 19. Docking studies were performed to explain reasons for the selective behavior of AChE inhibitors. Additionally, the quantitative structure-activity relationship (QSAR) and density functional theory (DFT) results of AChEs demonstrated that the size, shape, dipole moment, and ability to form hydrogen bond played the main role in both models. In addition, the aromatic π - π interactions and charge of the amide nitrogen had a major effect on insecticidal activity of the compounds. The present research can be helpful to gain a better understanding of the interactions between the insect AChE and its inhibitors and introduces compounds which are capable of becoming human-safe insecticides. SN - 1095-9939 UR - https://www.unboundmedicine.com/medline/citation/31153459/Synthesis,_crystal_structure,_insecticidal_activities,_molecular_docking_and_QSAR_studies_of_some_new_phospho_guanidines_and_phospho_pyrazines_as_cholinesterase_inhibitors L2 - https://linkinghub.elsevier.com/retrieve/pii/S0048-3575(19)30070-7 DB - PRIME DP - Unbound Medicine ER -